P426: A SINGLE-CENTER RETROSPECTIVE ANALYISIS OF THE MUTATIONAL PROFILE IN ACUTE MYELOID LEUKEMIA PATIENTS
Authors: Y. Martínez Díez, A. Franganillo Suárez, J. Cornago, L. Solan, R. Ayala, J. Martinez, P. Llamas, J. L. Lopez Lorenzo
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is a clonal disorder originating from specific genetic aberrations in myeloid precursor cells. Next generation sequencing (NGS) analyses provide clinicians with a deeper knowledge of AML pathogenesis and is being implemented as a routine test at diagnosis due to its relevance in management and prognosis, following the characterization of molecular subgroups. Here we provide a summary of our experience in a single centre (Fundación Jiménez Díaz University Hospital (FJDH), Madrid, Spain), describing the molecular profile of our AML patients, studied as part of a national Spanish project lead by the PETHEMA group, and an analysis on which alterations could be significant to overall survival (OS). Aims: Analyse prognosis associated to molecular profile of new cases of AML Methods: AML new diagnoses and relapses in FJDH from 2018 to 2020 were retrospectively evaluated. The samples were referred to a central laboratory (12 de Octubre University Hospital, Madrid, Spain) where NGS custom panels were run. Other significant variables were analysed. Results: 66 AML patients were evaluated with a mean age of 60yo (22-93). 191 mutations were detected and most NGS were run at diagnosis 57 (86.4%). Most of the sample received an intensive treatment 42 (63.6%), however only 25 (37.9%) patients achieved CR, 2 (3%) CRi, 6 (9.1%) +MRD, 4 (6.1%) PR and 26 (39.4%) were refractory. 11 (16.7%) patients relapsed. Median OS was 13 months (CI 95% 7.9 – 18.1). Survival analysis confirmed significant differences between the 3 ELN prognostic groups and some of the genetic alteration (Figure 1). In this series there was high incidence of secondary and adverse prognosis AML, as expected from the high expression of ASXL1 (12.1%) and TP53 (15.2%) mutations. DNMT3A mutations were most frequent (25.8%), followed by NPM1 (22.8%). We also found IDH mutations (28.8%), which though less common could also be expected in adverse prognosis AML. Our sample size was big enough that prognostic differences within each ELN classification group were observed, as well as related to treatment. There was statistical significance in OS between patients with wildtype vs mutated TP53 (8.9 vs 22.8; p=0.037) or JAK2 (3.8 vs 22.5, p=0.001), as supported by literature. Interestingly, we also found DNMT3A mutated AML had a worse OS (24.1 vs 12.7; p=0.023). This may support recommending HSCT in DNMT3A-mutated AML, as argued for TP53- and JAK2-mutated AML. Although our OS graphs inclined towards favourable prognosis in the presence of NPM1 mutations (27.9 vs 19.9; p=0.12) and adverse prognosis with ASXL1 (11.1 vs 22.5; p=0.055), the statistical analysis did not show significance in either case, probably due to small sample size. RUNX1 did not seem to play a role in prognosis (19.1 vs 20.4; p= 0.741) which might be because most patients underwent HSCT, although current studies seem to suggest RUNX1 mutations are independent to prognosis. Similarly, FLT3-ITD mutations did not confer worse outcomes (25.5 vs 20.1; p=0.464). This may be due to the mutation often being absent in disease relapse or progression, sometimes in relation to targeted therapies. In our sample IDH mutations did not confer changes to OS (18.2 vs 21.9; p=0.707), though this could be explained by the limited availability of targeted therapies in our country. Image:Summary/Conclusion: We found high incidence of high risk AML. Most of our data agree with the published literature. Of note, RUNX1 doesn’t seem to play an important role in prognosis. However, DNMT3A mutations alone and mainly as a group with TET2 and ASXL1 were related to a bad outcome.